1. Field of the Invention
The present invention relates generally to the fields of molecular biology and gene cloning. More specifically, the present invention relates to the identification and characterization of the gene encoding human cytoplasmic polyadenylation element binding protein and uses thereof.
2. Description of the Related Art
During meiotic maturation of human oocytes gene transcription is repressed (Braude et al., 1988) and required proteins are translated from pre-existing, maternally derived mRNAs (Pal et al., 1994). In model systems (Drosophila, Xenopus, and the mouse), certain maternally derived mRNAs which encode key regulators of cell cycle progression and pattern formation are translationally silent in immature oocytes and become translationally activated following hormonal stimulation (Davidson, 1986; Wickens et al., 1996). This translational activation has been correlated with the cytoplasmic polyadenylation of the mRNAs, a process directed by two elements within the mRNA 3′ untranslated region (UTR) (reviewed in Richter, 1999). The first element is the AAUAAA polyadenylation hexanucleotide and the second element is a uridine-rich sequence of general consensus UUUUUAU termed the cytoplasmic polyadenylation element (CPE). In addition to directing cytoplasmic polyadenylation and translational activation, these cytoplasmic polyadenylation element sequences have also been implicated in mediating translational repression in immature oocytes (de Moor and Richter, 1999; Barkoff et al., 2000; Tay et al., 2000) and during the early phases of hormonally stimulated oocyte maturation (Charlesworth et al., 2000). Cytoplasmic polyadenylation element-mediated mRNA translational control has also been suggested to occur in mammalian neuronal cells (Wu et al., 1998).
A cytoplasmic polyadenylation element binding protein, CPEB, has been cloned from a number of species (Hake and Richter, 1994; Gebauer and Richter, 1996; Bally-Cuif et al., 1998; Walker et al., 1999) and has been implicated in mediating both polyadenylation-dependent translational activation and cytoplasmic polyadenylation element-directed translational repression (Hake and Richter, 1994; Stebbins-Boaz et al., 1996; Stutz et al., 1998; Minshall et al., 1999; Stebbins-Boaz et al., 1999; Mendez et al., 2000). While it is not clear how the cytoplasmic polyadenylation element binding protein can exert these apparently opposite effects on mRNA translation, there is some evidence that the C-terminal domain is necessary for translational repression while the N-terminal domain may regulate translational activation. It has been reported that overexpression of an N-terminally truncated form of the Xenopus cytoplasmic polyadenylation element binding protein (lacking the first 139 amino acids) did not significantly affect translational repression but did block both cytoplasmic polyadenylation and translational induction (Mendez et al., 2000).
Given the key role of cytoplasmic polyadenylation in the control of mRNA translation in model organisms, it is of interest to determine if a similar process occurred in humans. However, human cytoplasmic polyadenylation element binding protein has not been identified. Thus, the prior art is deficient in identifying a human cytoplasmic polyadenylation element binding protein which is essential for the study of mRNA translation control in human. The present invention fulfills this long-standing need and desire in the art by cloning a human cytoplasmic polyadenylation element binding protein.